Molecular studies reveal that A134T,G156A and G1333A SNPs in the CD177 gene are associated with atypical expression of human neutrophil antigen‐2

Background and Objectives The human neutrophil antigen‐2 (HNA‐2) is expressed on a subpopulation of neutrophils as most subjects present a negative plus a positive HNA‐2 population of neutrophils. The number of neutrophils expressing HNA‐2 is variable and may increase in pregnancy, infections, myeloproliferative disorders and after G‐CSF. This study investigated the presence of polymorphisms in the gene encoding HNA‐2 (CD177) in individuals presenting different patterns of antigen expression and determined the association of single nucleotide polymorphisms (SNPs) with the heterogeneous HNA‐2 expression. Materials and Methods Flow cytometry was employed to analyse the HNA‐2 expression on neutrophils from 135 healthy subjects using two monoclonal antibodies (TAG4, 7D8). Sequencing reactions were performed on subjects whose antigen expression was low (≤ 50%), high (≥ 80%) or atypical (a nonreactive population plus two distinct positive cell populations). Results Five SNPs were detected, two of them (A793C, G1084A) were related to a low expression of HNA‐2 (P = 0·031 and P = 0·004). Atypical antigen expression was observed in 5·9% (8/135) of the individuals, three nonpregnant women and five men. In these cases, the cDNA sequences revealed three SNPs (A134T, G156A and G1333A) strongly related to this atypical HNA‐2 expression (P = 0·004, P = 0·006 and P < 0·0001, respectively). Conclusions Our data show that polymorphisms in the CD177 are associated with variations in the HNA‐2 expression and may be the cause of atypical expressions.